There are a significant number of viruses that can infect cattle. Such viruses include bovine viral diarrhea virus types 1 and 2, (BVDV1, or alternatively BVD1; and BVDV2, or alternatively BVD2), infectious bovine rinotracheitis (IBR) virus, parainfluenza type 3 (PI3), bovine respiratory syncytial virus (BRSV), Rift Valley fever virus (RVFV), and bovine respiratory coronavirus (BRCV). In addition, there are a number of bacteria that can infect cattle too, including Pasteurella multocida, Mannheimia haemolytica, Histophilus somni, and Mycoplasma bovis. 
It is now widely accepted that the best way of preventing disease due to bacterial or virus infections in bovine is to vaccinate them against these viruses. Moreover, multivalent live attenuated virus or bacterial vaccines can be safely administered that limit the number of vaccine injections required. Accordingly, there are commercially available multivalent live virus vaccines that protect against BVDV1 and BVDV2, IBR, PI3, and/or BRSV. However, heretofore, attenuated cattle viruses have been unstable when stored in liquid solutions. Therefore, most live attenuated bovine virus vaccines are lyophilized, i.e., freeze-dried, prior to their long-term storage. The live attenuated bovine virus is commonly mixed as a suspension in water with a protective agent, frozen, and then dehydrated by sublimation and secondary drying during the lyophilization process. The low temperatures of freezing and drying by sublimation, together with the low surface to volume ratios involved, can require long drying periods and thereby, significantly increase manufacturing time and costs.
In addition, there are inherent inconsistencies in large commercial drying processes due to: the inability to adjust the shelf temperature across the entire product load, variable freezing rates across the dryer, edge effects, and radiant energy effects. Increasing the drying temperature to reduce drying times is often not an option since the drying temperature has to remain significantly below the glass-transition temperature of the protective protein matrix. Moreover, the long inconsistent drying times and/or high drying temperatures often lead to structural damage to the live attenuated viruses, along with a significant loss of their biologic activity.
Consequently, in order to account for the inherent loss in efficacy, lyophilized bovine vaccines that comprise live attenuated viruses are stored with augmented titers. However, such increased titers can lead to significant adverse events should the lyophilization process actually lead to less loss of activity than anticipated. Therefore, great care is required to formulate a vaccine to contain a virus titer that is not only safely below the amount that leads to adverse events, but that also maintains sufficient efficacy in view of the virus titer loss due to lyophilisation and subsequent storage.
Furthermore, there is a limitation to the size of a lyophilisation vials and/or number of doses contained within such vials due to relatively small standard stopper sizes for the tops of these vials. Therefore, large volumes of liquid become difficult to sublimate through the relatively small openings. In addition, a large vial requires that the user to somehow transfer a large volume of diluent to the lyophilized cake in a sterile manner, whereas the rehydration of many more smaller vials is just inconvenient. Indeed, either alternative is particularly vexing in a feedlot environment where the vaccine recipients, e.g., the cattle, reside. Therefore, there is a need for new live attenuated bovine virus vaccines that can reliably retain their virus titers at a safe and efficacious level.
The citation of any reference herein should not be construed as an admission that such reference is available as “prior art” to the instant application.